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Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy
Simon Kraler1,2, Mark C Blaser3, Elena Aikawa3,4
1Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
European Heart Journal
|December 1, 2021
Summary
Calcific aortic valve disease (CAVD) involves progressive valve stiffening and narrowing. New research explores novel therapeutic targets beyond cholesterol lowering to treat this prevalent heart condition.
Area of Science:
- Cardiovascular Medicine
- Pathobiology
- Translational Therapeutics
Background:
- Calcific aortic valve disease (CAVD) is a common, progressive condition leading to aortic stenosis and heart failure.
- CAVD shares risk factors with atherosclerotic cardiovascular disease but has distinct molecular mechanisms.
- Statins are ineffective for treating CAVD, necessitating new therapeutic strategies.
Purpose of the Study:
- To delineate the key molecular and cellular mechanisms driving CAVD pathobiology.
- To identify novel therapeutic targets for non-invasive treatment of CAVD.
- To review emerging pharmaceutical strategies for altering CAVD progression.
Main Methods:
- Review of current literature on CAVD pathogenesis.
- Analysis of molecular and cellular mechanisms including endothelial dysfunction, lipid homing, and immune infiltration.
- Examination of phospho-calcium metabolism and valvular interstitial cell activation.
- Identification of potential therapeutic targets from recent phase II trials.
Main Results:
- CAVD pathogenesis involves endothelial barrier dysfunction, lipid accumulation, immune cell infiltration, and abnormal phospho-calcium metabolism.
- Valvular interstitial cells adopt myofibroblast/osteoblast-like properties, driving fibro-calcific remodeling.
- Several novel targets show promise for altering CAVD progression, including lipoprotein(a) and matrix Gla protein.
Conclusions:
- Understanding CAVD's unique pathobiology is crucial for developing effective treatments.
- Emerging targets offer hope for non-invasive therapeutic interventions.
- Future therapies may focus on modulating inflammation, osteogenesis, and lipid metabolism in the aortic valve.
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